FBXO22 is a potential therapeutic target for recurrent chondrosarcoma.

Chondrosarcoma (CHS) is a malignant bone tumor with insensitivity to both radiotherapy and chemotherapy, and a high recurrence rate. However, the latent mechanism of recurrent CHS (Re-CHS) remains elusive. Here, we discovered that FBXO22 was highly expressed in clinical samples of Re-CHS. FBXO22 played a significant role in various cancers. However, the role of FBXO22 in Re-CHS remained unclear. Our research demonstrated that suppressing FBXO22 abated the proliferation and migration of CHS cells and facilitated their apoptosis. In addition, suppressing FBXO22 raised the expression of PD-L1 in Re-CHS. All these findings provide new evidence for using FBXO22 and PD-L1 as combined targets to prevent and treat Re-CHS, which may prove to be a novel strategy for immunotherapy of CHS, especially Re-CHS.

The Application of Ultrasonography-Computed Tomography Fusion Navigation Technology in Complex Bone Tumor Biopsy: A Randomized Double-Blind Controlled Trial.

OBJECTIVE: This study aims to investigate the clinical application value of ultrasonography-computed tomography (CT) fusion navigation technology in bone tumor biopsy surgery. METHODS: Thirty patients with bone tumors requiring biopsy surgery were randomly assigned to either the U-C group (ultrasonography-CT group; n = 15) or the control group (n = 15). The U-C group used ultrasonography-CT fusion navigation technology for real-time localization of the biopsy needle, whereas the control group relied on intraoperative C-arm fluoroscopy for localization. The success rate of the surgeries, the number of radiation exposures during the procedure, surgical time, and intraoperative blood loss were compared between the 2 groups. RESULTS: The number of intraoperative radiation exposures in the U-C group was 2 versus 7 in the control group (P < 0.05), showing significant differences between the 2 groups. The success rate of biopsies in the U-C group and control group was 100% (P > 0.05), the mean operative time was 45 ± 9 minutes versus 42 ± 13 minutes (P > 0.05), and intraoperative bleeding volume was 10 ± 4 mL versus 11 ± 5 mL (P > 0.05), all showing no significant differences between the 2 groups. CONCLUSIONS: The real-time localization of the biopsy needle in bone tumor biopsy surgery using ultrasonography-CT fusion navigation technology can significantly reduce intraoperative radiation exposure for both patients and surgeons during the procedure. Consequently, this technique holds certain clinical applicability.

PRISMA-the 100 most-cited articles on chondrosarcoma recurrence: A bibliometric analysis.

BACKGROUND: Chondrosarcoma (CHS) is highly prone to recurrence and has become the most common malignant bone tumor in adults. The authors aim to identify and analyze the top 100 most-cited articles in this field, enabling researchers to quickly grasp the research focus and progress in the area of chondrosarcoma recurrence. METHODS: A search in the Web of Science database yielded a total of 305 articles related to CHS recurrence between 2013 and 2022. Filtering was done based on the titles and abstracts of the articles in the list, and the top 100 most-cited articles were selected. The following information were analyzed using bibliometric methods: article title, first author, year of publication, journal of publication, total citations, country, institution, and keywords. RESULTS: Among the selected 100 articles, the most frequently cited one has 224 citations. The most commonly appearing journals, institutions, and countries are as follows: "Clinical Orthopaedics Related Research" (5 times); Fudan University, University of Texas System, and Royal Orthopaedic Hospital (4 times each), with China and the USA cited the most (21 times each). The year 2018 is the most productive year (17 articles). About 97 first authors contributed one article each, and 3 had 2 articles each. Among all 229 keywords, the top 3 in frequency are CHS (20%), recurrence (4%), and surgery (3%). Twenty article topics are related to surgical treatment. CONCLUSION: Research on CHS recurrence is citation-rich but focuses more on treatments than understanding mechanisms, indicating a need for deeper mechanistic exploration for treatment breakthroughs in the future.

Risk Factors for Postoperative Surgical Site Infection in Patients Undergoing Spinal Tumor Surgery.

STUDY DESIGN: A retrospective comparative case-control study. OBJECTIVE: The aim of this study was to determine the risk factors for postoperative surgical site infection (SSI) in patients with spinal tumors requiring reoperation during the perioperative period. SUMMARY OF BACKGROUND DATA: SSI is a common postoperative complication of spinal surgery. The occurrence of SSI not only increases the mortality rate but prolongs the patient's hospital stay and increases the medical cost. METHODS: Included in this study were 202 patients with spinal tumors who received surgical treatment between January 2008 and December 2018, of whom 101 patients who developed SSI and underwent secondary surgery were used as the SSI group, and the other 101 patients with no SSI who were matched with the SSI group by age (±10), pathologic diagnosis (malignant/no-malignant), tumor site (C/T/L/S), surgical approach (anterior/posterior/combined), and surgical team were used as the control group. The clinical data of the 202 patients in both groups were analyzed by logistic regression modeling to identify SSI-associated risk factors. RESULTS: Multivariate logistic regression analysis showed that the revision status ( B =1.430, P =0.028), the number of spinal levels fused ≥4 ( B =0.963, P =0.006), and the use of bone cement ( B =0.739, P =0.046) were significantly associated with the increased risk of developing postoperative SSI. CONCLUSIONS: This study identified the revision status, the number of spinal levels fused ≥4, and the use of bone cement as independent risk factors for SSI in patients with spinal tumors who underwent reoperation during the perioperative period.

BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression.

Osteosarcoma (OS) is a bone tumour affecting adolescents. Dysregulation of Barx homeobox 1 (BARX1) expression is involved in various cancers, but its function and mechanism in the process of OS are undefined. This study revealed that BARX1 expression is higher in OS tissue than in adjacent normal tissue. Downregulation of BARX1 in OS cells significantly suppressed their proliferation and migration, whereas enforced expression of exogenous BARX1 exerted the opposite effects on OS cells. Subsequently, heat shock 70-kDa protein 6 (HSPA6) expression was clearly increased after BARX1 overexpression in OS cells, as confirmed by RNA sequencing. The dual-luciferase reporter assay confirmed that HSPA6 expression is directly regulated by BARX1. The in vitro assay indicated that silencing HSPA6 expression attenuated OS proliferation and migration induced by BARX1. A dual immunofluorescence labelling assay provided further evidence that BARX1 was overexpressed and associated with HSPA6 overexpression in OS tumour tissue. In conclusion, BARX1 promotes OS cell proliferation and migration by inducing the expression of HSPA6, which plays an oncogenic role in OS. BARX1 and HSPA6 can potentially act as novel therapeutic targets for OS.

Efficacy and safety of erythropoietin in isolated spinal metastasis patients with total en bloc spondylectomy surgery: a case-control study.

OBJECTIVE: The purpose of our study is to identify the effect of short-term and high-dose use of erythropoietin (EPO) in spinal isolated metastatic patients with Total en bloc spondylectomy (TES) surgery by assessing hematological parameters, transfusion volume, postoperative complications, recurrence-free survival (RFS), and overall survival (OS). METHODS: From January 2015 and January 2022, 93 isolated spinal metastasis patients were selected and separated into 2 groups based on the treatment method used (EPO + TXA (Tranexamic acid) group, n = 47; and TXA group, n = 46). Indexes for evaluation included hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, transfusion rate, and mean units transfused. RESULTS: The average follow-up duration was 38.13 months. There was no significant difference (P > 0.05) in RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, and transfusion rate between the two groups. However, patients in EPO + TXA group have significantly higher Hb, Hct, and RBC values than those in the TXA group on postoperative days 1, 2, 3, and 5. Moreover, the mean transfusion volume in EPO + TXA group was significantly lower than those in the TXA group (P = 0.011). CONCLUSIONS: Perioperative short-term and high-dose administration of EPO could improve the anemia-related hematological parameters and reduce the requirement for blood transfusion without increasing the risk of deep vein thrombosis and tumor progression in solitary spinal metastatic patients with TES surgery.

A Discussion on the Criteria for Surgical Decision-Making in Elderly Patients With Metastatic Spinal Cord Compression.

STUDY DESIGN: Retrospective study. OBJECTIVES: Although the role of surgery in the management of metastatic spinal cord compression (MSCC) has been well established, elderly patients may still be denied surgery because of higher risk of complications and shorter life expectancy. The purpose of this study was to determine whether elderly patients with MSCC could benefit from surgery and discuss the criteria for surgical decision-making in such patients. METHODS: Enrolled in this study were 55 consecutive patients aged 75 years or older who were surgically treated for MSCC in our center. Prognostic factors predicting overall survival (OS) were explored by the Kaplan-Meier method and Cox regression model. The quality of life (QoL) of the patients was evaluated by the SOSGOQ and compared using Student's t test. Risk factors for postoperative complications were identified by Chi-square test and multiple logistic regression analysis. RESULTS: Surgical treatment for MSCC substantially improved the neurological function in 55.8% patients and QoL in 88.5% patients with acceptable rates of postoperative complications (16.4%), reoperation (9.1%), and 30-day mortality (1.8%). Postoperative ECOG-PS of 1-2, total en-bloc spondylectomy (TES), and postoperative chemotherapy were favorable prognostic factors for OS, while a high Charlson Comorbidity Index (CCI) and a long operation time were risk factors for postoperative complications. CONCLUSIONS: Surgery should be encouraged for elderly patients with MSCC 1) who are compromised by the current or potential neurological dysfunction; 2) with radioresistant tumors; 3) with spinal instability; and 4) with no comorbidity, ECOG-PS of 0-2, and systemic treatment adherence. In addition, surgery should be performed by a skilled and experienced surgical team.

DJ-1 promotes osteosarcoma progression through activating CDK4/RB/E2F1 signaling pathway.

Osteosarcoma (OS) is a primary malignant tumor of the bone characterized by poor prognosis due to chemotherapy resistance and high recurrence rates. DJ-1 (PARK7) is known as an oncogene and its abnormal expression is related to the poor prognosis of various types of malignant tumors. It was found in this study that upregulated expression of DJ-1 was closely correlated with the prognosis of OS patients by promoting the proliferation, migration and chemotherapy resistance of OS cells in vitro through regulating the activity of CDK4 but not through the oxidation mechanism or AKT pathway. The combination of DJ-1 and CDK4 promoted RB phosphorylation, leading to the dissociation of E2F1 into the nucleus to regulate the expression of cell cycle-related genes. The tumor xenograft mouse model demonstrated that DJ-1 knockout suppressed tumor growth in vivo. All these findings indicate that DJ-1 can affect the occurrence and progression of OS by regulating the CDK/RB/E2F1axis, suggesting a novel therapeutic opportunity for OS patients.

Development and Validation of a Scoring System for Differential Diagnosis of Tuberculosis and Metastatic Tumor in the Spine.

PURPOSE: Spinal tuberculosis (TB) and metastatic tumor (MT) are common diseases with similar manifestations. Although pathological evaluation is the gold standard to confirm diagnosis, performing biopsies in all patients is not feasible. This study is aimed to create a scoring system to facilitate the differential diagnosis of spinal TB and MT before invasive procedures. METHODS: Altogether, 447 patients with spinal TB (n=198) and MT (n=249) were retrospectively analyzed. Patients were randomly assigned at 2:1 ratio to a training cohort and a validation cohort. Clinical, laboratory, and radiological diagnostic factors were identified by χ2 and multiple logistic regression analyses. The scoring system was then established based on the identified independent diagnostic factors scored by regression coefficient ß value, with the cut-off value being determined by ROC curve. The sensitivity and specificity of the system was calculated by comparing the predicted diagnosis with their actual pathological diagnosis. RESULTS: This scoring system was composed of 5 items: pain worsens at night (0 or 2 points), CRP value (0 or 3 points), tumor marker values (0 or 2 points), skip lesions (0 or 3 points), and intervertebral space destruction (0 or 3 points). Patients scoring higher than 7.5 could be diagnosed as spinal TB, otherwise, MT. According to the internal validation, the sensitivity and specificity of the system were 87.9% and 91.6%, respectively. CONCLUSION: This study established and validated a scoring system which could be used to differentiate spinal TB from MT, thus helping clinicians in quick and accurate differential diagnosis.

Biomechanical analysis of a novel height-adjustable nano-hydroxyapatite/polyamide-66 vertebral body: a finite element study.

BACKGROUND: To compare the biomechanical properties of a novel height-adjustable nano-hydroxyapatite/polyamide-66 vertebral body (HAVB) with the titanium mesh cage (TMC) and artificial vertebral body (AVB), and evaluate its biomechanical efficacy in spinal stability reconstruction. METHODS: A 3D nonliner FE model of the intact L1-sacrum was established and validated. Three FE models which instrumented HAVB, TMC, and AVB were constructed for surgical simulation. A pure moment of 7.5 Nm and a 400-N preload were applied to the three FE models in 3D motion. The peak von Mises stress upon each prosthesis and the interfaced endplate was recorded for analysis. In addition, the overall and intersegmental range of motion (ROM) of each model was investigated to assess the efficacy of each model in spinal stability reconstruction. RESULTS: AVB had the greatest stress concentration compared with TMC and HAVB in all motions (25.6-101.8 times of HAVB, 0.8-8.1 times of TMC). The peak stress on HAVB was 3.1-10.3% of TMC and 1.6-3.9% of AVB. The maximum stress values on L2 caudal and L4 cranial endplates are different between the three FE models: 0.9-1.9, 1.3-12.1, and 31.3-117.9 times of the intact model on L2 caudal endplates and 0.9-3.5, 7.2-31.5, and 10.3-56.4 times of the intact model on L4 cranial endplates in HAVB, TMC, and AVB, respectively, while the overall and segmental ROM reduction was similar between the three models, with AVB providing a relatively higher ROM reduction in all loading conditions (88.1-84.7% of intact model for overall ROM and 69.5-82.1% for L1/2, 87.0-91.7% for L2/4, and 71.1-87.2% for L4/5, respectively). CONCLUSIONS: HAVB had similar biomechanical efficacy in spinal stability reconstruction as compared with TMC and AVB. The material used and the anatomic design of HAVB can help avoid stress concentration and the stress shielding effect, thus greatly reducing the implant-associated complications. HAVB exhibited some advantageous biomechanical properties over TMC and AVB and may prove to be a potentially viable option for spinal stability reconstruction. Further in vivo and vitro studies are still required to validate our findings and conclusions.

Recurrence or neurological loss? Resection mode selection for patients with large sacral chordoma: an analysis of prognostic factors and quality of life.

BACKGROUND: Surgical resection represents the main therapeutic method for sacral chordoma, but plans for resection mode must weigh neurological loss against complete tumor excision, a difficult balance to strike. The purpose of this study was to provide useful information contributing to surgical decision making in sacral chordoma. METHODS: A retrospective review was performed on 47 patients with large sacral chordoma. Prognostic factors affecting recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Quality of life was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and compared using Student's t test. RESULTS: Resection mode was the independent prognostic factor affecting RFS, while independent prognostic factors affecting OS were resection mode and postoperative recurrence. As for quality of life, the en bloc resection group showed a higher score in emotional well-being, while the piecemeal resection group scored better in function well-being. No significant difference was identified in total the FACT-G score between two groups. CONCLUSIONS: On the one hand, en bloc resection showed huge advantages in disease control for sacral chordoma. On the other hand, despite the unsatisfaction in functional well-being, en bloc resection did not sacrifice quality of life significantly in terms of the total FACT-G score.

A Novel Height-Adjustable Nano-Hydroxyapatite/Polyamide-66 Vertebral Body for Reconstruction of Thoracolumbar Structural Stability After Spinal Tumor Resection.

BACKGROUND: Reconstruction of thoracolumbar structural stability is a formidable challenge for spine surgeons after vertebral body tumor resection. Various disadvantages of the currently used expandable or nonexpandable cages have limited their clinical applications. We sought to develop a novel prosthesis for clinical use and assess its preliminary clinical outcome in reconstruction of thoracolumbar structural stability after spinal tumor resection. METHODS: Using data obtained from a retrospective analysis of the morphological characteristics of the thoracolumbar vertebrae and endplates in previously reported studies, we modified the nano-hydroxyapatite/polyamide-66 (n-HA/PA66) strut into a novel height-adjustable vertebral body. A retrospective study was performed of 7 patients who had undergone reconstruction of thoracolumbar structural stability with this novel prosthesis from August 2016 to January 2017. RESULTS: A novel height-adjustable vertebral body (AHVB) composed of n-HA/PA66 with 2 separate components with a 163° contact surface at each end was manufactured. The height-adjustable range was 28-37 mm. No significant implant-related complications were observed in the process of operation. All patients experienced a significant reduction in pain, with the visual analog scale score decreasing from 7.9 to 4.0. Neurological improvement was assessed using the Frankel grading system after surgery. Postoperative radiographic and computed tomography/magnetic resonance imaging findings indicated that the operated segment was stable, the outcome of kyphosis correction was good, and no prosthesis subsidence or dislocation was observed. CONCLUSION: This novel prosthesis has many advantages in the reconstruction of height, lordosis, and alignment after thoracolumbar spinal tumor resection and has a favorable prospect for clinical application.

SOSTDC1 inhibits bone metastasis in non-small cell lung cancer and may serve as a clinical therapeutic target.

Bone metastasis occurs in ~40% patients with non­small cell lung cancer (NSCLC), resulting in serious morbidity and mortality. Sclerostin domain­containing protein 1 (SOSTDC1) has been demonstrated to be associated with the development and progression of multiple types of cancer. However, the role of SOSTDC1 in NSCLC bone metastasis remains unclear. In the present study, it was identified that SOSTDC1 was downregulated in NSCLC bone metastatic lesions compared with that in primary tumors, and low SOSTDC1 expression predicted poor prognosis for patients with NSCLC. Functionally, SOSTDC1 overexpression suppressed NSCLC cell proliferation, migration, invasion and cancer cell­induced osteoclastogenesis, while SOSTDC1 knockdown produced the opposite effect. In addition, a number of potential downstream target genes of SOSTDC1, which were demonstrated to be associated with tumor progression and bone metastasis, were identified in NSCLC cells by RNA deep sequencing and RT­qPCR assays. The results from the present study may provide useful insight for an improved understanding of the pathogenesis of NSCLC bone metastasis, and suggest that SOSTDC1 may be a potential prognostic biomarker and therapeutic target for NSCLC bone metastasis.

ILKAP Binding to and Dephosphorylating HIF-1α is Essential for Apoptosis Induced by Severe Hypoxia.

BACKGROUND/AIMS: Integrin-linked kinase-associated phosphatase (ILKAP), a serine/threonine phosphatase that belongs to the protein phosphatase 2C family, has a role in cell survival and apoptosis. Hypoxia-inducible factor 1α (HIF-1α) is the key transcription factor in the response to oxygen deficiency in mammals. Direct phosphorylation and dephosphorylation of HIF-1α affect its function. The present study investigated the role of ILKAP on HIF-1α dephosphorylation and cell behavior. METHODS: HIF-1α was induced by hypoxia. Physical binding between ILKAP and HIF-1α was demonstrated by a co-immunoprecipitation assay. HIF-1α transcriptional activity was investigated using a hypoxia-response element-containing luciferase reporter plasmid. Cell viability was evaluated by a trypan blue dye exclusion assay. ILKAP function was explored by a gain and loss assay with an overexpression plasmid and shRNA infection. RESULTS: ILKAP physically interacted with HIF-1α and induced its dephosphorylation. Both the HIF-1α-p53 interaction and apoptosis relied on ILKAP. CONCLUSION: The results indicated that the ILKAP directly binds and dephosphorylates HIF-1α and responsible for severe hypoxia-induced cell apoptosis.

COL5A1 may contribute the metastasis of lung adenocarcinoma.

BACKGROUND: Lung cancer leads to the largest number of cancer-related deaths worldwide and is usually accompanied with metastasis which is the primary cause of those death and correlated with poor prognosis. However, the mechanism of lung cancer metastasis is still lack of definition. METHODS: We compared the primary lung adenocarcinoma (AD) and its metastasis tissues induced by overexpression of KrasG12D and inactivation of P53 in mouse lungs by analyzing GSE40222 about the differentially expressed genes (DEGs), pathways and hub genes. And human lung AD databases are used to verify the conversed changes of identified key gene and then followed functional studies are performed to explore the functions of key gene. RESULTS: We identified 165 genes differentially expressed in lung AD metastasis compared to primary AD. Pathway analysis identified 649 GO biological processes and 8 KEGG pathways, such as ECM-receptor interaction. Biological network interaction identified the hub genes during lung adenocarcinoma metastasis, such as the up-regulated COL5A1, a novel gene in AD metastasis. We found it's also increased in human AD and advanced stage. Knockdown of COL5A1 in human AD metastatic cells inhibited cell growth and invasion, and induced cell apoptosis. Notably, higher expression of COL5A1 was observed in the lung AD patients with recurrence and short survive. CONCLUSION: By analyzing mouse lung AD and its metastases, we identified the potential key genes and pathways regulating lung AD metastasis, such as COL5A1. The following analysis of COL5A1 in human AD database and cells explores its functions, holding the implications of target therapy in AD metastasis and also providing more clues for future studies.